ID   GILT_HUMAN              Reviewed;         250 AA.
AC   P13284; Q76MF9; Q8NEI4; Q8WU77; Q9UL08;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 3.
DT   27-MAR-2024, entry version 173.
DE   RecName: Full=Gamma-interferon-inducible lysosomal thiol reductase;
DE            EC=1.8.-.- {ECO:0000269|PubMed:10639150, ECO:0000269|PubMed:10852914};
DE   AltName: Full=Gamma-interferon-inducible protein IP-30;
DE   AltName: Full=Legumaturain;
DE   Flags: Precursor;
GN   Name=IFI30; Synonyms=GILT, IP30;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX   PubMed=3136170; DOI=10.1016/s0021-9258(18)37889-x;
RA   Luster A.D., Weinshank R.L., Feinman R., Ravetch J.V.;
RT   "Molecular and biochemical characterization of a novel gamma-interferon-
RT   inducible protein.";
RL   J. Biol. Chem. 263:12036-12043(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, IDENTIFICATION BY MASS SPECTROMETRY, PROTEIN
RP   SEQUENCE OF N-TERMINUS, GLYCOSYLATION, AND MUTAGENESIS OF CYS-72 AND
RP   CYS-75.
RX   PubMed=10639150; DOI=10.1073/pnas.97.2.745;
RA   Arunachalam B., Phan U.T., Geuze H.J., Cresswell P.;
RT   "Enzymatic reduction of disulfide bonds in lysosomes: characterization of a
RT   gamma-interferon-inducible lysosomal thiol reductase (GILT).";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:745-750(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Arahira M., Fukazawa C.;
RT   "A novel Asn-bond specific endoproteolytic enzyme from Human.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-72 AND CYS-75, AND
RP   GLYCOSYLATION.
RX   PubMed=10852914; DOI=10.1074/jbc.m003459200;
RA   Phan U.T., Arunachalam B., Cresswell P.;
RT   "Gamma-interferon-inducible lysosomal thiol reductase (GILT). Maturation,
RT   activity, and mechanism of action.";
RL   J. Biol. Chem. 275:25907-25914(2000).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
CC   -!- FUNCTION: Lysosomal thiol reductase that can reduce protein disulfide
CC       bonds. May facilitate the complete unfolding of proteins destined for
CC       lysosomal degradation. Plays an important role in antigen processing.
CC       Facilitates the generation of MHC class II-restricted epitodes from
CC       disulfide bond-containing antigen by the endocytic reduction of
CC       disulfide bonds (By similarity). Facilitates also MHC class I-
CC       restricted recognition of exogenous antigens containing disulfide bonds
CC       by CD8+ T-cells or crosspresentation (By similarity). {ECO:0000250}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1200 uM for F(ab')2 fragment when denatured
CC         {ECO:0000269|PubMed:10639150};
CC         KM=10 uM for F(ab')2 fragment {ECO:0000269|PubMed:10639150};
CC         Note=Kinetic parameters shown are for mature enzyme.;
CC       pH dependence:
CC         Optimum pH is 4-5. {ECO:0000269|PubMed:10639150};
CC   -!- SUBUNIT: Dimer; disulfide-linked. {ECO:0000269|PubMed:10852914,
CC       ECO:0000269|PubMed:3136170}.
CC   -!- INTERACTION:
CC       P13284; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-2868897, EBI-739863;
CC       P13284; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2868897, EBI-945833;
CC       P13284; P22735: TGM1; NbExp=3; IntAct=EBI-2868897, EBI-2562368;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10639150,
CC       ECO:0000269|PubMed:3136170}. Lysosome {ECO:0000269|PubMed:10639150,
CC       ECO:0000269|PubMed:3136170}.
CC   -!- INDUCTION: Expressed constitutively in antigen-presenting cells and
CC       induced by IFN-gamma in other cell types. {ECO:0000269|PubMed:3136170}.
CC   -!- PTM: N-glycosylated. Sugar chains contain mannose-6-phosphate.
CC       {ECO:0000269|PubMed:10639150, ECO:0000269|PubMed:10852914}.
CC   -!- PTM: Synthesized as a 35 kDa precursor which is then processed into the
CC       mature 30 kDa form via cleavage of N-terminal and C-terminal
CC       propeptides. Processing of the precursor is mediated by multiple
CC       lysosomal proteases.
CC   -!- MISCELLANEOUS: Both precursor form and mature form have thiol reductase
CC       activity.
CC   -!- SIMILARITY: Belongs to the GILT family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA36105.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAA36105.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAA36105.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. N-terminal sequence identical to a region of chromosome 11.; Evidence={ECO:0000305};
CC       Sequence=AAF04618.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. N-terminal sequence identical to a region of chromosome 11.; Evidence={ECO:0000305};
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DR   EMBL; J03909; AAA36105.1; ALT_SEQ; mRNA.
DR   EMBL; AF097362; AAF04618.1; ALT_SEQ; mRNA.
DR   EMBL; AB049659; BAC98466.1; -; mRNA.
DR   EMBL; AC007192; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC068499; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471106; EAW84662.1; -; Genomic_DNA.
DR   EMBL; BC021136; AAH21136.1; -; mRNA.
DR   EMBL; BC031020; AAH31020.1; -; mRNA.
DR   CCDS; CCDS46015.1; -.
DR   PIR; A43708; A43708.
DR   RefSeq; NP_006323.2; NM_006332.4.
DR   AlphaFoldDB; P13284; -.
DR   SMR; P13284; -.
DR   BioGRID; 115704; 87.
DR   IntAct; P13284; 32.
DR   MINT; P13284; -.
DR   STRING; 9606.ENSP00000384886; -.
DR   GlyConnect; 1262; 18 N-Linked glycans (2 sites).
DR   GlyCosmos; P13284; 3 sites, 17 glycans.
DR   GlyGen; P13284; 5 sites, 17 N-linked glycans (2 sites).
DR   iPTMnet; P13284; -.
DR   PhosphoSitePlus; P13284; -.
DR   BioMuta; IFI30; -.
DR   DMDM; 327478582; -.
DR   EPD; P13284; -.
DR   jPOST; P13284; -.
DR   MassIVE; P13284; -.
DR   MaxQB; P13284; -.
DR   PaxDb; 9606-ENSP00000384886; -.
DR   PeptideAtlas; P13284; -.
DR   ProteomicsDB; 52905; -.
DR   Pumba; P13284; -.
DR   Antibodypedia; 27932; 194 antibodies from 29 providers.
DR   DNASU; 10437; -.
DR   Ensembl; ENST00000407280.4; ENSP00000384886.1; ENSG00000216490.4.
DR   GeneID; 10437; -.
DR   KEGG; hsa:10437; -.
DR   MANE-Select; ENST00000407280.4; ENSP00000384886.1; NM_006332.5; NP_006323.2.
DR   UCSC; uc002nic.3; human.
DR   AGR; HGNC:5398; -.
DR   CTD; 10437; -.
DR   DisGeNET; 10437; -.
DR   GeneCards; IFI30; -.
DR   HGNC; HGNC:5398; IFI30.
DR   HPA; ENSG00000216490; Tissue enhanced (lung, lymphoid tissue).
DR   MIM; 604664; gene.
DR   neXtProt; NX_P13284; -.
DR   OpenTargets; ENSG00000216490; -.
DR   PharmGKB; PA29644; -.
DR   VEuPathDB; HostDB:ENSG00000216490; -.
DR   eggNOG; KOG3160; Eukaryota.
DR   GeneTree; ENSGT00390000010450; -.
DR   HOGENOM; CLU_066886_0_1_1; -.
DR   InParanoid; P13284; -.
DR   OMA; SHKEVCF; -.
DR   OrthoDB; 91276at2759; -.
DR   PhylomeDB; P13284; -.
DR   TreeFam; TF315141; -.
DR   PathwayCommons; P13284; -.
DR   Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR   Reactome; R-HSA-877300; Interferon gamma signaling.
DR   SignaLink; P13284; -.
DR   SIGNOR; P13284; -.
DR   BioGRID-ORCS; 10437; 20 hits in 1160 CRISPR screens.
DR   ChiTaRS; IFI30; human.
DR   GeneWiki; IFI30; -.
DR   GenomeRNAi; 10437; -.
DR   Pharos; P13284; Tbio.
DR   PRO; PR:P13284; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; P13284; Protein.
DR   Bgee; ENSG00000216490; Expressed in monocyte and 96 other cell types or tissues.
DR   ExpressionAtlas; P13284; baseline and differential.
DR   GO; GO:0030054; C:cell junction; IDA:HPA.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR   GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR   GO; GO:0016667; F:oxidoreductase activity, acting on a sulfur group of donors; IMP:UniProtKB.
DR   GO; GO:0016671; F:oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor; IEA:InterPro.
DR   GO; GO:0042590; P:antigen processing and presentation of exogenous peptide antigen via MHC class I; ISS:UniProtKB.
DR   GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR   GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl.
DR   GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR   InterPro; IPR004911; Interferon-induced_GILT.
DR   PANTHER; PTHR13234; GAMMA-INTERFERON INDUCIBLE LYSOSOMAL THIOL REDUCTASE GILT; 1.
DR   PANTHER; PTHR13234:SF8; GAMMA-INTERFERON-INDUCIBLE LYSOSOMAL THIOL REDUCTASE; 1.
DR   Pfam; PF03227; GILT; 1.
DR   Genevisible; P13284; HS.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW   Lysosome; Oxidoreductase; Redox-active center; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   PROPEP          27..57
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000269|PubMed:10639150"
FT                   /id="PRO_0000021328"
FT   CHAIN           58..232
FT                   /note="Gamma-interferon-inducible lysosomal thiol
FT                   reductase"
FT                   /id="PRO_0000021329"
FT   PROPEP          233..250
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000269|PubMed:10639150"
FT                   /id="PRO_0000021330"
FT   CARBOHYD        63
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        95
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        108
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        72..75
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000269|PubMed:10639150,
FT                   ECO:0000269|PubMed:10852914"
FT   MUTAGEN         72
FT                   /note="C->S: Abolishes reducing activity, does not affect
FT                   dimerization. Abolishes reducing activity; when associated
FT                   with S-75."
FT                   /evidence="ECO:0000269|PubMed:10639150,
FT                   ECO:0000269|PubMed:10852914"
FT   MUTAGEN         75
FT                   /note="C->S: Abolishes reducing activity, does not affect
FT                   dimerization. Abolishes reducing activity; when associated
FT                   with S-72."
FT                   /evidence="ECO:0000269|PubMed:10639150,
FT                   ECO:0000269|PubMed:10852914"
FT   CONFLICT        76
FT                   /note="R -> Q (in Ref. 7; AAH31020)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        98
FT                   /note="L -> S (in Ref. 1; AAA36105)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        119
FT                   /note="H -> L (in Ref. 1; AAA36105)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        148
FT                   /note="C -> WHG (in Ref. 1; AAA36105)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        223
FT                   /note="T -> A (in Ref. 3; BAC98466)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   250 AA;  27964 MW;  54B4950E3788CD5A CRC64;
     MTLSPLLLFL PPLLLLLDVP TAAVQASPLQ ALDFFGNGPP VNYKTGNLYL RGPLKKSNAP
     LVNVTLYYEA LCGGCRAFLI RELFPTWLLV MEILNVTLVP YGNAQEQNVS GRWEFKCQHG
     EEECKFNKVE ACVLDELDME LAFLTIVCME EFEDMERSLP LCLQLYAPGL SPDTIMECAM
     GDRGMQLMHA NAQRTDALQP PHEYVPWVTV NGKPLEDQTQ LLTLVCQLYQ GKKPDVCPSS
     TSSLRSVCFK
//